Clinical Relevance of Interleukin-6 in Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease: A Systematic Review with Meta-analysis
Bryan Rudas Sulca1, Gerardo Luna-Peralta2, Alvaro Milla-Martinez1, Freddy Arcos Rivera1, Ivan Alegre-Cordero1, Leonardo Di Cosmo3, Danielle Kei Pua4
1Sociedad Científica de San Fernando, Universidad Nacional Mayor de San Marcos, Lima, Perú, 2Universidad Nacional Mayor de San Marcos, Lima, Perú, 3Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy, 4Westchester Medical Center, New York, USA
Objective:
To summarize the current evidence on the levels of interleukin-6 (IL-6) in cerebrospinal fluid (CSF) and serum of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).
Background:
IL-6 is implicated in MOGAD's pathophysiology, but data on its levels in CSF and serum, and its clinical significance, remain limited. Understanding IL-6 levels may aid in its role as a potential biomarker for MOGAD.
Design/Methods:
A systematic search of five databases (PubMed, Embase, Scopus, Web of Science, and Google Scholar) was conducted until September 2025. Observational studies measuring IL-6 in CSF and serum of MOGAD patients were included. Meta-analysis using Standardized Mean Difference (SMD) with a random-effects model was applied to estimate pooled effects. A narrative synthesis was provided when meta-analysis was not possible. Risk of bias was assessed using the Newcastle-Ottawa scale.
Results:
Seven studies (621 patients) were included. CSF IL-6 levels were significantly elevated in MOGAD compared to controls (SMD = 2.72; 95% CI 0.15 to 5.29; I² = 95.2%). Comparisons with MS showed no significant differences in serum (MD = 0.68; 95% CI –1.18 to 2.54; I² = 87.3%), but a significant difference in CSF (SMD = 0.78; 95% CI 0.44 to 1.12; I² = 0%). Comparisons with NMOSD showed no significant differences in serum (MD = –0.58; 95% CI –1.14 to –0.01; I² = 0%) or CSF (SMD = 0.16; 95% CI –0.28 to 0.60; I² = 0%). All studies showed a low risk of bias.
Conclusions:
IL-6 levels in CSF are elevated in MOGAD compared to controls, though high heterogeneity in studies limits generalizability. IL-6 showed significant differences in CSF between MOGAD and MS, but not with NMOSD. These findings suggest that IL-6 may not be a reliable biomarker for MOGAD, especially in serum. Further research with larger samples and standardized methodologies is needed to confirm its clinical utility.
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